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At least 1,153 records · Page 64Linked to original sources
PubMed2003

A two-arm phase II study of temozolomide in patients with advanced gastrointestinal stromal tumors and other soft tissue sarcomas.

BACKGROUND: The authors conducted a two-arm Phase II study of temozolomide to determine its efficacy and toxicity in patients with soft tissue sarcomas (STSs) who had received, had refused, or were not eligible for standard chemotherapy with doxorubicin and ifosfamide (Arm 1) and in patients with gastrointestinal stromal tumors (GISTs; Arm 2). Patients with GIST were eligible regardless of prior therapy before imatinib was available. METHODS: Sixty patients were enrolled in the current study, 19 of whom had GISTs and 41 of whom had other STSs. The patients received temozolomide at a dose of 85 mg/m2 orally for 21 days followed by 7 days without treatment. Standard radiographic imaging after every two cycles was used to assess the treatment response. RESULTS: Of the 39 patients in Arm 1, there was 1 complete response and 1 partial response of 39 evaluable patients, for a total response rate of 5% (95% confidence interval, 0-12%). The responses lasted 7 months and 8 months, respectively. In Arm 2, there was no response in 17 patients. The disease was stable in 22% of the patients with GISTs and 33% of the patients with other STSs. The median overall survival time was 26.4 months in patients with GISTs and 11 months in patients with other STSs. The median time to disease progression was 2.3 months in patients with GISTs and 3.3 months in patients with other STSs. Grade 3 and Grade 4 adverse effects (according to National Cancer Institute Common Toxicity Criteria) were rare and included fatigue (eight patients), anemia (six patients), constipation (four patients), neutropenia (four patients), and thrombocytopenia (four patients). CONCLUSIONS: The data from the current study suggest that temozolomide is well tolerated but has only minimal efficacy and a limited role in the treatment of patients with STSs.

Administration, Oral↗
PubMed2001

Alteration of chromosome arm 6p is characteristic of primary mediastinal B-cell lymphoma, as identified by genome-wide allelotyping.

Five cases of primary mediastinal B-cell lymphoma (PMBL) each have been studied with 375 microsatellite markers from all 22 autosomes. Of the 151 genomic alterations among the 1,875 assays, only five were allelic losses. The remainder of the microsatellite alterations consisted of 114 allelic imbalances and 32 instabilities. Microsatellite alterations were found in all cases on chromosomal arms 6p and 9p. These allelic imbalances most likely are indicative of genetic amplification, a finding agreeing well with those of studies using either comparative genomic hybridization or arbitrarily primed polymerase chain reaction, in which amplification of chromosome arm 9p in PMBL has been found. The allelic imbalances on chromosome arm 6p always included marker D6S276 located at 6p21.3-p22.3, where the MHC class I genes reside. These allelic imbalances may be reflective of alterations in the expression of the MHC gene products, characteristic of PMBL. Allelic anomalies close to the MYB gene locus on 6q were detected in two cases and prompted the analysis of MYB rearrangements in a series of 30 lymphomas. One rearrangement was detected in one of 18 cases of PMBL and in none of 10 diffuse, large B-cell lymphomas and two T-cell lymphomas. Our genome-wide microsatellite analysis provides independent confirmation that PMBL is characterized by infrequent chromosomal losses and by frequent genetic alterations involving chromosomal arm 9p. For the first time, chromosomal arm 6p has been identified as a highly frequent target of genetic alterations in this tumor type. Finally, MYB may also be involved occasionally in PMBL pathogenesis.

Alleles↗
PubMed1988

Utilization of digital image processing to study dynein arms (ATPase) in normal and immotile cilia.

Tracheal ciliary cross sections were examined with scanning transmission electron microscopy and the resultant images were digitized for image enhancement. A gray-scale histogram of each ciliary image was produced and manipulated to enhance the image for dynein arms. Tracheal epithelial tissue from the pig, rabbit, and dog, including dogs with immotile cilia syndrome, was examined by using this technique. Tissue from each animal was fixed with each of three different fixatives and sections were evaluated for preservation of dynein arms. The same fixative did not consistently provide optimal fixation for ciliary dynein arms in all three species examined. Each species, therefore, must be evaluated to determine the optimal fixative for preservation of normal ciliary ultrastructure. Digital image processing provides a mechanism for enhancing dynein arms in situ without the need for addition of special stains or the use of techniques such as image summation. With this technique it has been shown that about two-thirds of outer dynein arms are partially or completely missing on cilia from dogs with immotile cilia syndrome.

Adenosine Triphosphatases↗
PubMed2001

Biophysical evidence of arm-domain interactions in AraC.

We report development of a method for the direct measurement of the interaction between the N-terminal arm and the remainder of the dimerization domain in the Escherichia coli AraC protein, the regulator of the l-arabinose operon. The interaction was measured using surface plasmon resonance to monitor the association between the immobilized peptide arm and the dimerization domain, truncated of its arm, in solution. As expected from genetic and physiological data, the interaction is strongly stimulated by l-arabinose and is insensitive to sugars like d-glucose or d-galactose. Alterations in the sequence of the arm which physiological experiments predict either to strengthen or weaken the arm produce the expected responses.

Amino Acid Sequence↗
PubMed1994

Merosin promotes neurite growth and Schwann cell migration in vitro and nerve regeneration in vivo: evidence using an antibody to merosin, ARM-1.

Monoclonal antibodies that block the cellular function(s) of specific antigens can provide valuable probes for in vitro and in vivo bioassays. With the goal of understanding the molecular basis of neuron-Schwann cell interactions during development and regeneration, we have sought antibodies that interfere with the function of merosin, the predominant laminin isoform present in the Schwann cell basement membrane. To identify the biological functions of merosin in the peripheral nervous system, we studied Schwann cell migration and neurite outgrowth in vitro and nerve regeneration in vivo, in the presence and the absence of a monoclonal antibody that we believe binds to merosin, ARM-1 (Anti Rodent Merosin-1). The ARM-1 antibody blocked both neurite outgrowth and Schwann cell migration in vitro. This antibody also reduced neuritic branching in vitro. In vivo, the ARM-1 antibody blocked the regeneration of sympathetic nerve fibers in the rat iris. The blockade of neurite outgrowth and Schwann cell migration by ARM-1 antibody suggests that merosin is involved in facilitating the two most critical cellular events during the normal development and regeneration of peripheral nerves, i.e., axon growth and Schwann cell migration. Furthermore, the regulation of both Schwann cell migration and axon growth by the ARM-1 antigen implies that these two cellular events obey a common set of molecular signals during the development and regeneration of peripheral nerves.

Animals↗
PubMed1999

Directional Converter Arm Method for Surface and Interfacial Tension Measurements with a Top-Loading Balance.

A method is described for utilizing a top-loading balance, with a directional converter arm, in vertical-pull surface force measurements. The Padday rod-pull technique, the du Noüy ring method, and the Wilhelmy plate method are utilized with rods, thin-walled tubes, wire rings, and plates either rigidly attached to the converter arm or hanging freely from a hook at the end of the arm. The robustness, large weighing capacity, and accuracy of top-loading balances make them ideally suited for a variety of types of surface and interfacial tension measurements. The converter arm method can be used with a stainless steel rod (3-7 mm in diameter) in vertical-pull surface tension measurements, with samples having volumes of only a few tenths of a milliliter. Measurements on very small liquid volumes are feasible because the rod is firmly attached to the converter arm rather than hanging freely as in measurements with balances mounted above the sample; therefore, the rod cannot swing toward and attach to the wall of small sample tubes. Automation of force and height measurements with the converter arm/top-loading balance method is straightforward. Copyright 1999 Academic Press.

Journal Article↗
PubMed1996

Assembly and orientation of Flp recombinase active sites on two-, three- and four-armed DNA substrates: implications for a recombination mechanism.

The normal recombination reaction catalyzed by the Flp (pronounced flip) site-specific recombinase between two full-site DNA substrates requires the action of four recombinase monomers in concert. Each monomer of the recombinase harbors an incomplete active site, and is hence chemically incompetent. In order to organize the strand cleavage pocket, it must accept the catalytic tyrosine (Tyr 343) from a second Flp monomer. We address the issue of the potential modes of assembling the shared active site in substrates containing two, three or four Flp binding arms. In normal full-sites (two Flp binding arms), strand cleavage occurs within a substrate and not across substrates. Flp is able to resolve a Y structure (three Flp binding arms) into linear plus hairpin recombinants. Strand cleavage by Flp in a Y structure and in a Holliday structure (four Flp binding arms) follows the trans rather than the cis mode. Within the context of two normal full-sites, all of the strand cutting patterns are best accommodated by a single-cleavage mode, namely the trans-horizontal mode. The assembly and orientation of a Flp active site is determined by whether two Flp-bound DNA arms have the stacking flexibility to accommodate the relevant protein-protein interactions. These results provide support for a model in which pairs of monomers bound within each of the two DNA partners contribute to the strand cleavage reactions that initiate and terminate a normal recombination event. Thus all four Flp monomers are required to mediate the cleavage/joining events at either end of the strand exchange region.

Base Sequence↗
PubMed1998

Arm-domain interactions in AraC.

N-terminal deletions extending beyond the sixth amino acid of the Escherichia coli regulator of the l-arabinose operon, AraC, were found to generate constitutive regulatory behavior of the promoter pBAD. Mutagenesis of the DNA coding for the first 20 amino acids of the protein and screening for constitutives yielded mutants across the region whereas screening for mutants that cannot induce pBAD, even in the presence of arabinose, yielded none. These results indicate that the N-terminal arm is not essential for transcription activation, but that it plays an important and active role in holding the system in a non-activating state. Despite the fact that arabinose binds to the N-terminal domain of AraC, mutations were found in the C-terminal domain that weaken the binding of arabinose to the protein. The effects of the mutations could be suppressed by specific mutation in the N-terminal arm or by deletion of the arm. These results, in conjunction with the crystal structures of the N-terminal domain determined in the presence and absence of arabinose, indicate that in the absence of arabinose, the N-terminal arms of the protein bind to the C-terminal DNA binding domains to hold them in a state where the protein prefers to loop. When arabinose is added, the arms are pulled off the C-terminal domains, thereby releasing them to bind to adjacently located DNA half-sites and activate transcription.

AraC Transcription Factor↗
PubMed2001

Positively charged residues at the N-terminal arm of the homeodomain are required for efficient DNA binding by homeodomain-leucine zipper proteins.

Plant homeodomain-leucine zipper proteins, unlike most animal homeodomains, bind DNA efficiently only as dimers. In the present work, we report that the deletion of the homeodomain N-terminal arm (first nine residues) of the homeodomain-leucine zipper protein Hahb-4 dramatically affects its DNA-binding affinity, causing a 70-fold increase in dissociation constant. The addition of the N-terminal arm of Drosophila Antennapedia to the truncated form restores the DNA-binding affinity of dimers to values similar to those of the native form. However, the Antennapedia N-terminal arm is not able to confer increased binding affinity to monomers of Hahb-4 lacking the leucine zipper motif, indicating that the inefficient binding of monomers must be due to structural differences in other parts of the molecule. The construction of proteins with modifications at residues 5 to 7 of the homeodomain suggests strongly that positively charged amino acids at these positions play essential roles in determining the DNA-binding affinity. However, the effect of mutations at positions 6 and 7 can be counteracted by introducing a stretch of positively charged residues at positions 1 to 3 of the homeodomain. Sequence comparisons indicate that all homeodomain-leucine zipper proteins might use contacts of the N-terminal arm with DNA for efficient binding. The occurrence of a homeodomain with a DNA-interacting N-terminal arm must then be an ancient acquisition in evolution, earlier than the separation of lines leading to metazoa, fungi and plants.

Amino Acid Sequence↗
PubMed2000

Detection of the swings of the lever arm of a myosin motor by fluorescence resonance energy transfer of green and blue fluorescent proteins.

The "lever-arm" model of a myosin motor predicts that the lever-arm domain in the myosin head tilts and swings against the catalytic domain during ATP hydrolysis, resulting in force generation. To investigate if this "swing" of the lever arm really occurs during the hydrolysis of ATP, we employed fluorescence resonance energy transfer (FRET) between two fluorescent proteins [green (GFP) and blue (BFP)] fused to the N and C termini of the Dictyostelium myosin-motor domain. FRET measurements showed that the C-terminal BFP in the fusion protein first swings against the N-terminal GFP at the isomerization step of the ATP hydrolysis cycle and then swings back at the phosphate-release step. Because the C-terminal BFP mimics the motion of the lever arm, the result indicates that the lever arm swings at the specific steps of the ATP hydrolysis cycle, i.e., at the isomerization and phosphate-release steps. The latter swing may correspond to the power stroke of myosin, while the former may be related to the recovery stroke.

Adenosine Diphosphate↗
PubMed1993

The distal hindlimb musculature of the cat: multiaxis moment arms at the ankle joint.

The cat hindlimb muscles have been classified, traditionally, as flexors and extensors, based on their actions in the parasagittal plane and their patterns of recruitment during locomotion and reflex responses. This study provides a detailed examination of the relative magnitudes of the various moment arms of the cat ankle muscles and the interdependent effects of position in the various axes of motion. We used a method based on observing small sliding movements of tendon in response to small angular displacements of the joint. Surprisingly, we found that the ankle joint of the cat permits substantial motion in three axes (eversion/inversion and abduction/adduction as well as extension/flexion) and many muscles crossing the ankle joint have their largest moment arms about axes other than extension/flexion. These moment arms often depended on the joint position in the axis of the moment arm and, to a lesser degree, on the extension/flexion angle as well. For some muscles (notably peroneus longus) there was sufficient variability that the predominant action in neutral posture (axis with the largest moment arm) could change from animal to animal, which may be related to heterogeneities of locomotor and reflex recruitment reported in the companion paper.

Animals↗
PubMed1982

The coordination of eye, head, and arm movements during reaching at a single visual target.

The time of occurrence of eye, head, and arm movements directed at the same visual target was measured in five human subjects. The latency of activation of the corresponding neck and arm muscles was also measured. It appears that although the overt movements are sequentially ordered (starting with the eye movement, then the head and finally the arm) the EMG discharges are synchronous with respect to the eye movement onset. In addition, eye movement latency appears definitely (though weakly) correlated with either neck or arm EMG latencies. Neck and arm EMG latencies are also mutually correlated. These results indicate a clustering of segmental motor programs for target oriented actions.

Adult↗
PubMed1995

Colour contrast sensitivity in patients with soft drusen, an early stage of ARM.

The present institutional study was undertaken in order to determine whether testing of colour contrast sensitivity is valuable in detecting early functional changes in patients at initial stages of age-related maculopathy (ARM). The study included 27 patients with soft drusen as an early sign of ARM and 29 age-matched normals. The area occupied by drusen was determined using a computer program. Colour contrast sensitivity was measured with a computer graphics system. Visual acuity, central visual field (Humphrey Field Analyser) and colour vision (D-15 panel) were normal in both groups. Mean colour contrast sensitivity was significantly lower in patients with early ARM (for the protan axis: p = 0.00019, for the deutan axis: p = 0.000078 and for the tritan axis: p = 0.000096) than in the controls. Interindividual variations were large. There was a tendency towards a bimodal distribution for all three colour axes, most evident for the tritan axis. We found a correlation of the drusen area with the protan and deutan thresholds for the fundus colour photographs r = 0.5 (p < 0.01) and r = 0.4 (p < 0.05), respectively, and with the tritan threshold for the angiograms r = 0.5 (p < 0.05). The findings suggest that colour contrast sensitivity may offer an additional possibility of predicting exudative ARM. Whether the patients with the highest thresholds are those who will be the first to show progression with indications of exudative ARM is not yet known. The patient group will be followed up in order to elucidate this question.

Aged↗
PubMed2004

Associated anomalies with anorectal malformation (ARM).

OBJECTIVE: To find the prevalence of associated anomalies in children with anorectal malformation (ARM). METHODS: One hundred and forty patients (80 males and 60 females) with expand were studied to detect associated anomalies and to find their prevalence. High and low type of ARM was seen in 52.14% and 47.86% of patients respectively. Associated anomalies were more common with high type of ARM (78.08%) than in patients with low type of ARM (37.31%). 58.57% patients had associated anomalies which included those of urinary system (37.14%), vertebral system (34.28%), skeletal system other than vertebral (15.17%), genital system (14.29%), cardiovascular system (12.14%), gastrointestinal tract (10.7%) and spinal cord (10%). RESULTS: 37.43% patients had 3 or more than 3 components of VACTERL association. Two patients had all six components of VACTERL. Most common association was vertebral, anal and renal anomalies seen in 16 patients. CONCLUSION: Patients with ARM should undergo a detailed general physical, systemic and radiological examination (infanto-gram, echocardiography, US of urogenital system) in neonatal period to detect associated anomalies in early period.

Anal Canal↗
PubMed2004

Reduced metaphase I associations between the short arms of homologous chromosomes in a Hordeum vulgare L. x H. bulbosum L. diploid hybrid influences the frequency of recombinant progeny.

Hordeum vulgare (cultivated barley) x H. bulbosum (bulbous barley grass) hybrids have been used to obtain disease-resistant recombinant lines (RLs). The RLs contain chromatin transferred from the wild species mostly onto the long arms of recipient barley chromosomes. To determine whether differences in meiotic metaphase I (MI) associations between the long and short arms of homologous chromosomes can account for the preponderance of introgressions on the long arms, we carried out fluorescent in situ hybridisation on MI chromosome preparations obtained from pollen mother cells of a diploid interspecific hybrid. By using various probes, we established that MI associations between the long arms occurred more frequently than between the short arms for the five chromosomes tested.

Chromosome Pairing↗
PubMed2005

Cutaneous reflexes during rhythmic arm cycling are insensitive to asymmetrical changes in crank length.

The neural control of a movement depends upon the motor task performed. To further understand the neural regulation of different variations of the same type of movement, we created three dissimilar bilateral rhythmic arm cycling tasks by unilaterally manipulating crank length (CL). Modulation in the amplitude and sign of cutaneous reflexes was used as an index of neural control. Neurologically intact subjects performed three bilateral cycling trials at approximately 1 Hz with the ipsilateral crank arm at one of three different lengths. Cutaneous reflexes were evoked during each trial with trains (5 x 1.0 ms pulses at 300 Hz) of electrical stimulation delivered to the superficial radial nerve at the ipsilateral wrist. EMG recordings were made bilaterally from muscles acting at the shoulder, elbow, and wrist. Analysis was conducted after phase-averaging contingent upon the timing of stimulation in the movement cycle. CL variation created an asymmetrical cycling pattern and produced significant changes in the range of motion at the ipsilateral shoulder and elbow. Background EMG amplitude in muscles of the contralateral arm generally increased significantly as CL decreased. Therefore at a given phase in the movement cycle, the background EMG was different between the three cycling trials. In contrast, cutaneous reflex amplitudes in muscles of both arms were similar at each phase of the movement cycle between the different CLs trials at both early and middle latencies. This was particularly evident in muscles ipsilateral to nerve stimulation. We suggest that variations of arm cycling that primarily yield significant changes in the amplitude of muscle activity do not require significant task-specific change in neural control.

Adult↗
PubMed1998

Long-term follow-up of the clinical relevance of short outer dynein arms in human nasal cilia.

Clinical significance of short outer dynein arms was examined in a long-term follow-up study of 76 patients with various respiratory symptoms. Clinical evaluations, nasal mucociliary transport rate (NMTR) measurement and transmission electron microscopy were performed. Follow-up examinations took place 5-11 years later. In the initial examination four patients and on follow-up seven patients were found to have short outer dynein arms in their nasal mucosal biopsies. Short dynein arms were associated with a slow NMTR, poorly coordinated ciliary beat direction, and clinical symptoms of perennial rhinitis and recurrent sinusitis. Short dynein arms were found to be a significant histologic finding and probably represent a variant of primary ciliary dyskinesia. In some cases short outer dynein arms may be a reversible finding with improving clinical symptoms. It is obvious that at least part of dynein defects are acquired.

Adolescent↗
PubMed2005

Afuni, a novel transforming growth factor-beta gene is involved in arm regeneration by the brittle star Amphiura filiformis.

The bone morphogenetic proteins (BMPs) are a family of the transforming growth factor-beta (TGF-beta) superfamily that perform multiple roles during vertebrate and invertebrate development. Here, we report the molecular cloning of a novel BMP from regenerating arms of the ophiuroid Amphiura filiformis. The theoretically translated amino acid sequence of this novel BMP has high similarity to that of the sea urchin BMP univin. This novel BMP has been named afuni. Whole-mount in situ hybridisation implicates afuni in arm regeneration. Expression occurs in distinct proximal and distal regions of late regenerates (3- and 5-week postablation). These sites are at different stages of regeneration, suggesting multiple roles for this gene in adult arm development. Cellular expression of this gene occurs in migratory cells within the radial water canal (RWC) of regenerating and nonregenerating arms. These migrating coelomocytes suggest a key role for the coelomic RWC as a source of the cellular material for use in arm regeneration by A. filiformis.

Amino Acid Sequence↗